18-12884076-G-C

Variant names:

• chr18-12884076-G-C
• NM_002828.4:c.66C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002828.4(PTPN2):​c.66C>G​(p.Tyr22*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPN2 NM_002828.4 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.624
• Publications: 0 publications found

Genes affected

PTPN2 (HGNC:9650): (protein tyrosine phosphatase non-receptor type 2) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN2	NM_002828.4	MANE Select	c.66C>G	p.Tyr22*	stop_gained	Exon 1 of 9	NP_002819.2	P17706-1
	PTPN2	NM_001207013.2		c.66C>G	p.Tyr22*	stop_gained	Exon 1 of 11	NP_001193942.1	P17706-4
	PTPN2	NM_080422.3		c.66C>G	p.Tyr22*	stop_gained	Exon 1 of 10	NP_536347.1	P17706-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN2	ENST00000309660.10	TSL:1 MANE Select	c.66C>G	p.Tyr22*	stop_gained	Exon 1 of 9	ENSP00000311857.3	P17706-1
	PTPN2	ENST00000591115.5	TSL:1	c.66C>G	p.Tyr22*	stop_gained	Exon 1 of 11	ENSP00000466936.1	P17706-4
	PTPN2	ENST00000327283.7	TSL:1	c.66C>G	p.Tyr22*	stop_gained	Exon 1 of 10	ENSP00000320298.3	P17706-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.54	D
PhyloP100		0.62
Vest4		0.60
GERP RS		3.5
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr18-12884075;